SummaryPurpose: Stereotactic radiosurgery (SRS) has emerged as a viable alternative to surgery in the management of men-ingioma through exploiting the advantage of being mini-mally invasive with few complications and acceptable lo-cal control rates. The aim of this study was to evaluate the efficiency of linear accelerator (LINAC)-based SRS in the management of meningiomas and to report our experience using this sophisticated technique.

Methods: Between July 1998 and March 2012, 79 patients (42 female, 37 male) were treated using LINAC-based SRS in the Department of Radiation Oncology, Gulhane Mili-

tary Medical Academy. Median dose was 13 Gy (range 10-16) prescribed to the 80-95% isodose line encompassing the target.

Results: Median follow-up time was 53 months (range 9-112). Median tumor volume was 3.43 cc (range 0.3-14.1). Local tumor control was 89.7% in the 68 patients with ad-equate follow-up.

Conclusion: LINAC-based SRS offers a safe and effective treatment alternative to surgery in intracranial meningi-omas with high local control rates and low morbidity.

Key words: linear accelerator, meningioma, stereotactic radiosurgery

Evaluation of linear accelerator-based stereotactic radiosurgery in the management of meningiomas: a single center experienceF. Dincoglan, M. Beyzadeoglu , O. Sager, B. Uysal, S. Demiral, H. Gamsiz, B. DiricanDepartment of Radiation Oncology, Gulhane Military Medical Academy, Ankara, Turkey

Correspondence to: Ferrat Dincoglan, MD. Gulhane Military Medical Academy, Department of Radiation Oncology, Gn. Tevfik Saglam Cad. 06018, Etlik, Kecioren, Ankara, Turkey. Tel: +90 312 304 46 84, Fax:+90 312 304 46 80, E-mail: ferhatdincoglan@gmail.com Received: 24/01/2013; Accepted: 11/02/2013

Introduction

Meningiomas arise from the arachnoid cap cells and account for 30% of all central nervous system tumors [1-3]. In World Health Organiza-tion (WHO) classification, meningiomas are clas-sified as benign (WHO grade I), atypical (WHO grade II), and anaplastic or malignant (WHO grade III) meningiomas regarding their features includ-ing mitosis, hypercellularity, loss of architecture, spontaneous necrosis and brain invasion [4,5]. Meningiomas are usually well-circumscribed, homogeneous lesions which are easily diagnosed with non-invasive imaging methods [6]. Based on the study of Simpson et al. in 1957, gross total resection of meningiomas with involved dura and bone is suggested [7], however, for lesions such as skull base meningiomas, the close proximity of the tumor to critical structures including crani-al nerves or the optic pathways usually preclude

complete surgical resection despite advances in microsurgery [8,9]. It is estimated that complete surgical resection is not possible in 20-30% of the patients [10]. In addition, some patients are poor candidates for surgical approach considering their comorbidities which increase the risk of surgical resection. Even in case of gross total resection, recurrence rates have been reported to be in the range of 4-14% and 18-25% at 5 and 10 years, re-spectively [10,11] notwithstanding the gold stand-ard still being complete surgical removal in suit-able patients [10,12,13].

Radiotherapy may be used in both the adju-vant and definitive setting for meningiomas. Frac-tionated external radiotherapy is effectively used as adjuvant therapy in partially resected cases while it may also be used in unresectable men-ingiomas resulting in high local control rates of 70-80% at 10 years [14,15]. External beam radio-therapy has been shown to reduce postoperative

ORIGINAL ARTICLE

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recurrences, however it may have long-term det-rimental effects due to excess exposure of optic pathways and hypophysis in addition to potential cognitive function impairment [16,17].

With recent advances in the discipline of ra-diation oncology such as intensity modulated radiation therapy (IMRT), stereotactic radiosur-gery (SRS), and fractionated stereotactic radiation therapy (FSRT) allowing more precise treatments, improved local control with lower toxicity profile is achieved. SRS offers an alternative treatment option for the management of patients deemed unsuitable for surgery, and confers 5 and 10 year tumor control rates comparable to surgery, par-ticularly in skull base meningiomas [18]. Utiliza-tion of SRS in the management of meningiomas since 1990s for both the primary and adjuvant settings has conferred satisfactory control rates ranging between 86 and 100% [19-29]. In this study, we evaluated the efficiency of LINAC-based SRS in the management of meningiomas.

Methods

Between July 1998 and March 2012, patients with meningiomas were treated using LINAC-based sin-gle-dose SRS in the Department of Radiation Oncology, Gulhane Military Medical Academy. Informed consent of all patients was taken before the SRS treatment. De-tails of the SRS procedure were published previously [30-33]. For the first 10 years (1998-2008), cone-based SRS planning was performed with XKnife-3 (Radion-ics, Boston, MA, USA) and treatment was delivered by LINAC SL-25 with circular cones (Elekta, UK). In 2008, Xknife-3 radiosurgery planning system was replaced with ERGO ++ (CMS, Elekta, UK) planning system al-lowing Volumetric Modulated Arc Radiosurgery, and treatments were started to be delivered by LINAC Syn-ergy (Elekta, UK) with 3 mm thickness head-on micro multileaf collimator (mMLC). On the day of treatment, a stereotactic frame (Leksell frame or Brown-Roberts-Wells frame) was affixed with 4 pins to the patient’s skull under local anesthesia. Contrast-enhanced CT im-ages with 1.25 mm slice thickness were acquired by computed tomography (CT)-simulator (GE Lightspeed RT, GE Healthcare, Chalfont St. Giles, UK). Acquired images were sent to the workstation (SimMD, GE, UK) for contouring of target volume and critical structures. CT images were fused with T1 contrast-enhanced volu-metric MRI images, which were acquired 1 day before the treatment day. With the help of fusion, we took ad-vantage of both CT and MRI modalities to better local-ize the target and critical structures. Coronal and sag-ittal images were used in addition to axial images to improve target and organ-at-risk (OAR) delineation ac-curacy. After completion of contouring, structure sets including the target volume and OARs were transferred

to the treatment planning system (ERGO++ planning system, Elekta or XKnife-3, Radionics) to perform ra-diosurgery planning. SRS treatment planning was done with 6 MV photons with either a mMLC of 3 mm-thick leaves or SRS circular cone collimators. In the mMLC-based intensity modulated SRS planning using the vol-umetric-modulated arc therapy (VMAT) technique, arc modulation optimization algorithm (AMOA) was used to avoid exceeding OAR (i.e optic nerves, optic chiasm, brainstem) dose constraints and to improve dose ho-mogeneity within the target volume. Figure 1 shows axial, coronal, and sagittal treatment planning images of a patient with meningioma in ERGO planning sys-tem. Figure 2 shows a pre-SRS axial MR images of the patient in Figure 1. Figure 3 shows a post-SRS 3rd year follow-up axial MR images of the same patient.

In the planning, either a single 360-degree arc, double 360-degree arcs, or five 180-degree arcs were used to optimize OAR sparing. Median marginal dose was 13 Gy (range 10-16) prescribed to the 80-95% iso-dose line encompassing the target volume. Isocenters of all patients undergoing mMLC-based SRS were checked by image guided radiation therapy (IGRT) techniques including kV-CBCT (kilovoltage Cone Beam CT) and X-ray Volumetric Imaging (XVI, Elekta, UK) system. Eight mg intravenous dexamethasone with H2-antihistamines were used immediately after SRS. After completion of the SRS procedure, follow-up visits were scheduled for every patient routinely at 3-month intervals for the first year, at 6-month intervals for the second year, and annually thereafter including clinical examination with neurological evaluation and neuro-imaging with contrast-enhanced MRI. Follow-up tu-mor sizes measured for each patient were compared with pre-SRS measurements to assess local tumor control which was defined as no tumor enlargement or presence of tumor downsizing on follow-up imaging. Patients were requested to inform the treating physi-cian about any unexpected neurological worsening re-gardless of the follow-up schedule.

Results

A total of 79 patients referred to our depart-ment between July 1998 and March 2012 received LINAC-based SRS. The median patient follow-up time was 53 months (range 9-112). Forty-two pa-tients (53.2%) were female and 37 (46.8%) male. Median age was 41.1 years (range 23-74). Thir-ty out of the total 79 patients (37.9%) underwent surgery or biopsy before SRS; of these 30 patients, the type of operation was total resection in 10 (12.6%) patients, subtotal resection in 12 (15.2%), and biopsy in 8 (10.1%). Indication for post-sur-gery SRS was the presence of recurrent tumor in all 10 patients undergoing total resection, and the presence of residual tumor in the remaining

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Figure 3. Post-SRS 3rd year follow-up axial MR images of the patient in Figure 1 showing lesion downsizing (arrow).

Figure 2. Pre-SRS axial MR images of the patient in Figure 1 showing the meningioma (arrow).

Figure 1. Axial (A), coronal (B), and sagittal (C) treatment planning images of a patient with meningioma in ERGO planning system.

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20 patients. Median tumor volume for the total 79 patients was 3.43 cc (range 0.3-14.1). Out of the total 79 patients undergoing SRS, 46 patients (58.2%) were treated using cone collimators in the first 10 years (1998-2008) and 33 patients (41.8%) received mMLC-based SRS between 2008 and 2012. Of the total 79 patients 49 (62.1%) were diagnosed radiologically whereas 30 (37.9%) had

histopathologically verified diagnosis. Of the 30 patients with histopathological diagnosis 22 had WHO grade I and 8 WHO grade II meningiona. Periodical follow-up with serial MRI for at least 4 years was available in 68 of 79 patients (86%). Assessment of 68 patients with periodical fol-low-up MRI revealed unchanged tumor size in 38 patients (55.9%), tumor downsizing in 23 (33.8%), and tumor upsizing in 7 (10.3%). Thus, the pre-defined local tumor control rate was 89.7% in the 68 patients with periodical follow-up neuroim-aging. Of the 7 patients with tumor upsizing, en-largement of tumor after SRS occurred within 24 months in 3 of them, and later than 36 months in 4. Of these 7 patients with tumor upsizing, 5 un-derwent surgery, one patient underwent a second SRS session and one patient underwent external radiotherapy. Five out of 68 patients (7.4%) with adequate follow-up experienced morbidities (per-itumoral edema in 4 and radiation necrosis in 1 patient) following SRS which resolved after med-ical treatment. Of the 68 patients having symp-toms before SRS, 32 patients (47.1%) experienced clinical improvement, 29 (42.6%) had no change in symptoms and 7 (10.3%) had deterioration of the symptoms at follow-up. Out of the 32 patients with clinical improvement in preSRS symptoms, 19 patients suffered from headaches, 10 had sei-zures, 1 had diplopia, 1 had numbness in the face and 1 leg weakness, all of whom had alleviated symptoms in the postSRS follow-up period. Pa-tient characteristics are shown in Table 1.

Discussion

In this study, using LINAC-based SRS, we ob-served alleviation in preSRS symptoms including headache, seizures, diplopia, facial numbness, leg weakness and high local control of the menin-gioma lesions. In the management of surgically accessible intracranial meningiomas, gross total resection remains the mainstay of treatment. Ex-tent of surgical resection is associated with long-term local control. In the study by Mirimanoff et al., rates of freedom from recurrence for totally resected lesions were 93, 80, and 68% at 5, 10, and 15 years, respectively, whereas these rates were 63, 45, and 9% in the setting of subtotal resection [10]. Total surgical removal of meningiomas is achieved in 26-86% of the cases, and local recurrence rates are as high as 25% despite gross total resection [10]. Convexity meningiomas are frequently totally re-sected, however complete resection is rarely achiev-able in parasellar and sphenoidal meningiomas, re-sulting in high rates of recurrence. Recurrence rates

Table 1. Patient characteristics

Characteristics N %

Number of lesions 79 100

Median age, years (range) 41.1 (23-74)

GenderMaleFemale

3742

46.853.2

Surgery before SRSSubtotal Gross totalBiopsyNone

12108

49

15.212.610.162.1

Diagnosis By imagingHistopathologically

4930

62.137.9

WHO grade III

228

27.810.1

Previous radiotherapy None -

Presenting symptomsHeadache SeizureCranial nerve deficitDizziness Motor deficitHearing lossSensory deficitOther None

2617655423

11

3321.5

86652.54

14

Tumor localization Parasagittal/falx Convexity Cavernous sinusPetroclival Cerebellopontine angleOther

27181165

12

34.222.813.9

7.66.3

15.2

Median RT dose (range) 13 Gy (10-16)

Median tumor volume, cc (range) 3.43 (0.3-14.1)

Local tumor control (%) 89.7

Symptoms after SRSClin. improvementNo changeDeterioration

32297

47.142.610.3

MorbiditiesPeritumoral edemaNecrosis

41

5.91.5

SRS: stereotactic radiosurgery, RT: radiotherapy

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References1. Claus EB, Bondy ML, Schildkraut JM, Wiemels JL,

Wrensch M, Black PM. Epidemiology of intracranial meningioma. Neurosurgery 2005; 57: 1088-1095.

2. Bondy M, Ligon BL. Epidemiology and etiology of in-tracranial meningiomas: A review. J Neurooncol 1996; 29: 197-205.

3. Rigau V, Zouaoui S, Mathieu-Daude H et al. French brain tumor database (FBTDB): five years histological results on 25.756 cases. Brain Pathol 2011; 21: 633-644.

4. Beyzadeoglu M, Ozyigit, G, Ebruli C. Basic Radia-tion Oncology. In: Beyzadeoglu M, Ozyigit, G, Ebru-li C (Eds): Central nervous system tumors (1st Edn). Springer-Verlag, Berlin Heidelberg 2010, pp 175-203.

5. Kleihues P, Louis DN, Scheithauer BW et al. The WHO classification of tumors of the nervous system. J Neu-ropathol Exp Neurol 2002; 61: 215-225; discussion 226-219.

6. DiBiase SJ, Chin LS. Stereotactic radiosurgery for be-nign neoplasms. Tech Cancer Res Treatment 2003; 2: 127–133.

7. Simpson D. The recurrence of intracranial meningi-omas after surgical treatment. J Neurol Neurosurg Psychiatry 1957; 20: 22-39.

8. Dufour H, Muracciole X, Métellus P, Régis J, Chinot O, Grisoli F. Long-term tumor control and functional outcome in patients with cavernous sinus meningi-omas treated by radiotherapy with or without previ-ous surgery: Is there an alternative to aggressive tu-

may reach 100% after subtotal resection with pro-longed follow-up [34].

Significant developments in radiation tech-niques enable improved critical organ sparing with more homogeneous dose distributions. These developments in the technique improve lo-cal control and decrease morbidity. SRS is consid-ered to be an effective treatment modality since it is minimally invasive compared to surgery with few complications and acceptable local control rates. In the studies by Kondziolka and Flickinger; Gamma Knife radiosurgery achieved a local con-trol rate of 93% in the management of patients with meningioma [18,35]. Pollock et al. compared upfront SRS with surgery in the management of small and medium-sized meningiomas in all lo-cations, and found equivalent tumor control rates with SRS compared to Simpson grade 1 resec-tion at 3 and 7 years [36] . SRS conferred superior progression free survival (PFS) than surgery in the setting of less complete resections (Simpson grade 2-4) at 3 and 7 years [36] .

Including the “dural tail” in the treatment field for SRS is controversial due to the irradia-tion of larger fields and less conformal treatment plannings which led us to exclude dural tail in our treatment fields. However, some studies reported higher disease free survival (DFS) rates by includ-ing the dural tail in the treatment field. In the study by Dibiase et al., 5-year DFS was superior in patients with dural tail included in treatment field (96.0 vs 77.9% , p=0.038) [22]. However, in our study we found local tumor control compara-ble with many studies as 89.7% [20-29].

Tumor volume has been shown to be a predic-

tor for success with radiosurgery. DiBiase and col-leagues reported 5-year disease-free intervals of 91.9% for patients with tumors of 10 cc or small-er vs 68% for larger tumors [22]. Kondziolka et al. similarly reported a decreased control rate for larger tumors [37]. In our study, of the 7 patients with local failure, 5 had tumors larger than 10 cc.

FSRT is a viable treatment modality to treat lesions larger than 3 cm and in close proximity to critical structures. Han et al. reported no sig-nificant difference in the radiographic and clinical response in patients with skull base meningiomas treated with either SRS or FSRT [38].

SRS is not devoid of complications. Morbidi-ties including radiation necrosis, peritumoral ede-ma, cranial nerve deficits, delayed hydrocephalus may occur despite the low risk of complications at the time of the treatment. Zada et al. rewieved their experience using SRS in the management of meningiomas with an overall complication rate of 8% [39]. In our study, symptomatic peritumoral edema was observed in 4 patients and radiation necrosis in one patient. These 5 patients benefited from steroid treatment.

Conclusion

LINAC-based SRS offers a safe and effective alternative treatment modality to surgery in in-tracranial benign meningiomas with high local control rates and low morbidity. Its efficiency in particularly inaccessible lesions around critical re-gions at risk makes it an invaluable non-invasive modality for patients suffering from meningioma.

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mor removal? Neurosurgery 2001; 48: 285–296.

9. Van Havenbergh T, Carvalho G, Tatagiba M, Plets C, Samii M. Natural history of petroclival meningiomas. Neurosurgery 2003; 52: 55–62.

10. Mirimanoff RO, Dosoretz DE, Linggood RM, Ojemann RG, Martuza RL. Meningioma: Analysis of recurrence and progression following neurosurgical resection. J Neurosurg 1985; 62: 18 –24.

11. DeMonte F, Smith HK, al-Mefty O. Outcome of ag-gressive removal of cavernous sinus meningiomas. J Neurosurg 1994; 81: 245–251.

12. Marks SM, Whitwell HL, Lye RH. Recurrence of men-ingiomas after operation. Surg Neurol 1986; 25: 436–440.

13. Beks JF, de Windt HL. The recurrence of supratento-rial meningiomas after surgery. Acta Neurochirurgica 1988; 95: 3–5.

14. Miralbell R , Linggood RM, de la Monte S, Convery K, Munzenrider JE, Mirimanoff RO. The role of radio-therapy in the treatment of subtotally resected benign meningiomas. J Neurooncol 1992; 13: 157–164.

15. Maguire PD, Clough R, Friedman AH, Halperin EC. Fractionated external-beam radiation therapy for meningiomas of the cavernous sinus. Int J Radiat On-col Biol Phys 1999; 44: 75–79.

16. Goldsmith BJ, Rosenthal SA, Wara WM, Larson DA. Optic neuropathy after irradiation of meningioma. Radiology 1992; 185: 71–76.

17. Maire JP, Caudry M, Guérin J et al. Fractionated radia-tion therapy in the treatment of intracranial meningi-omas: local control, functional efficacy, and tolerance in 91 patients. Int J Radiat Oncol Biol Phys 1995; 33: 315–321.

18. Igaki H, Maruyama K, Koga T et al. Stereotactic radio-surgery for skull base meningioma. Neurol Med Chir 2009; 49: 456-461.

19. Kondziolka D, Lunsford LD, Coffey RJ, Flickinger JC. Stereotactic radiosurgery of meningiomas. J Neuro-surg 1991; 74: 552–559.

20. Kondziolka D, Mathieu D, Lunsford LD et al. Radio-surgery as definitive management of intracranial meningiomas. Neurosurgery 2008; 62: 53–60.

21. Lee JY, Niranjan A, McInerney J, Kondziolka D, Flick-inger JC, Lunsford LD. Stereotactic radiosurgery pro-viding long-term tumor control of cavernous sinus meningiomas. J Neurosurg 2002; 97: 65–72.

22. DiBiase SJ, Kwok Y, Yovino S et al. Factors predicting local tumor control after gamma knife stereotactic ra-diosurgery for benign intracranial meningiomas. Int J Radiat Oncol Biol Phys 2004; 60: 1515–1519.

23. Han JH, Kim DG, Chung HT et al. Gamma knife radio-surgery for skull base meningiomas: long-term radi-ologic and clinical outcome. Int J Radiat Oncol Biol Phys 2008; 72: 1324–1332.

24. Kreil W, Luggin J, Fuchs I, Weigl V, Eustacchio S, Pa-paefthymiou G. Long term experience of gamma knife radiosurgery for benign skull base meningiomas. J Neurol Neurosurg Psychiatry 2005; 76: 1425–1430.

25. Friedman WA, Murad GJ, Bradshaw P et al. Linear

accelerator surgery for meningiomas. J Neurosurg 2005; 103: 206–209.

26. Kimball MM, Friedman WA, Foote KD, Bova FJ, Chi YY. Linear accelerator radiosurgery for cavernous si-nus meningiomas. Stereotact Funct Neurosurg 2009; 87: 120–127.

27. Kollová A, Liscák R, Novotný J Jr, Vladyka V, Simon-ová G, Janousková L. Gamma Knife surgery for benign meningioma. J Neurosurg 2007; 107: 325–336.

28. Malik I, Rowe JG, Walton L, Radatz MW, Kemeny AA. The use of stereotactic radiosurgery in the man-agement of meningiomas. Br J Neurosurg 2005; 19: 13–20.

29. Kalogeridi MA, Georgolopoulou P, Kouloulias V, Kou-varis J, Pissakas G. Long-term follow-up confirms the efficacy of linac radiosurgery for acoustic neuroma and meningioma patients. A single intitution’s expe-rience. J BUON 2010; 15:68-73.

30. Surenkok S, Sager O, Dincoglan F et al. Stereotactic radiosurgery in pituitary adenomas: a single center experience. Int J Hematol Oncol 2012; 22: 255-260.

31. Dincoglan F, Sager O, Gamsız H et al. Management of arteriovenous malformations by stereotactic radio-surgery: a single center experience. Int J Hematol On-col 2012; 22: 107-112.

32. Dincoglan F, Sager O, Gamsız H et al. Stereotactic radiosurgery for intracranial tumors: a single center experience. Gulhane Med J 2012; 54: 190-198.

33. Sirin S, Oysul K, Surenkok S et al. Linear accelera-tor-based stereotactic radiosurgery in recurrent glio-blastoma: a single center experience. Vojnosanit Pregl 2011; 68: 961-966.

34. Barbaro NM, Gutin PH, Wilson CB, Sheline GE, Bol-drey EB, Wara WM. Radiation therapy in the treat-ment of partially resected meningiomas. Neurosur-gery 1987; 20: 525–528.

35. Flickinger JC, Kondziolka D, Maitz AH, Lunsford LD. Gamma knife radiosurgery of imaging-diagnosed in-tracranial meningioma. Int J Radiat Oncol Biol Phys 2003; 56: 801–806.

36. Pollock BE, Stafford SL, Utter A, Giannini C, Schreiner SA. Stereotactic radiosurgery provides equivalent tu-mor control to Simpson Grade 1 resection for patients with small- to medium-size. Int J Radiat Oncol Biol Phys 2003; 55: 1000-1005.

37. Kondziolka D, Flickinger JC, Perez B. Judicious resec-tion and/or radiosurgery for parasagittal meningi-omas. Outcomes from a multicenter review. Gamma Knife Meningioma Study Group. Neurosurgery 1998; 43: 405-414.

38. Han J, Girvigian MR, Chen JC et al. A Comparative Study of Stereotactic Radiosurgery, Hypofractionat-ed, and Fractionated Stereotactic Radiotherapy in the Treatment of Skull Base Meningioma. Am J Clin On-col 2012; Dec 13. [Epub ahead of print]

39. Zada G, Pagnini PG, Yu C et al. Long-term outcomes and patterns of tumor progression after gamma knife radiosurgery for benign meningiomas. Neurosurgery 2010; 67: 322-328.